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MSP-RON Signaling Is Activated in the Transition From Pancreatic Intraepithelial Neoplasia (PanIN) to Pancreatic Ductal Adenocarcinoma (PDAC)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest epithelial malignancies and remains difficult to treat. Pancreatic intraepithelial neoplasias (PanINs) represent the majority of the pre-cancer lesions in the pancreas. The PDAC microenvironment consists of activated pancreatic stellate...

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Autores principales: Li, Ce, Morvaridi, Susan, Lam, Gloria, Chheda, Chintan, Kamata, Yoshiko, Katsumata, Makoto, Edderkaoui, Mouad, Yuan, Xiaopu, Nissen, Nicholas, Pandol, Stephen J., Wang, Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399467/
https://www.ncbi.nlm.nih.gov/pubmed/30863319
http://dx.doi.org/10.3389/fphys.2019.00147
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author Li, Ce
Morvaridi, Susan
Lam, Gloria
Chheda, Chintan
Kamata, Yoshiko
Katsumata, Makoto
Edderkaoui, Mouad
Yuan, Xiaopu
Nissen, Nicholas
Pandol, Stephen J.
Wang, Qiang
author_facet Li, Ce
Morvaridi, Susan
Lam, Gloria
Chheda, Chintan
Kamata, Yoshiko
Katsumata, Makoto
Edderkaoui, Mouad
Yuan, Xiaopu
Nissen, Nicholas
Pandol, Stephen J.
Wang, Qiang
author_sort Li, Ce
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest epithelial malignancies and remains difficult to treat. Pancreatic intraepithelial neoplasias (PanINs) represent the majority of the pre-cancer lesions in the pancreas. The PDAC microenvironment consists of activated pancreatic stellate cells (PSCs) and immune cells, which are thought to contribute to neoplastic transformation. However, the signaling events involved in driving the transition from the neoplastic precursor to the more advanced and aggressive forms in the pancreas are not well understood. Recepteur d’Origine Nantais (RON) is a c-MET family receptor tyrosine kinase that is implicated in playing a role in cell proliferation, migration and other aspects of tumorigenesis. Macrophage stimulating protein (MSP) is the ligand for RON and becomes activated upon proteolytic cleavage by matriptase (also known as ST14), a type II transmembrane serine protease. In the current study, by immunohistochemistry (IHC) analysis of human pancreatic tissues, we found that the expression levels MSP and matriptase are drastically increased during the transition from the preneoplastic PanIN stages to the more advanced and aggressive PDAC. Moreover, RON is highly expressed in both PDAC and in cancer-associated stellate cells. In contrast, MSP, RON, and matriptase are expressed at low levels, if any, in normal pancreas. Our study underscores an emerging role of MSP-RON autocrine and paracrine signaling events in driving malignant progression in the pancreas.
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spelling pubmed-63994672019-03-12 MSP-RON Signaling Is Activated in the Transition From Pancreatic Intraepithelial Neoplasia (PanIN) to Pancreatic Ductal Adenocarcinoma (PDAC) Li, Ce Morvaridi, Susan Lam, Gloria Chheda, Chintan Kamata, Yoshiko Katsumata, Makoto Edderkaoui, Mouad Yuan, Xiaopu Nissen, Nicholas Pandol, Stephen J. Wang, Qiang Front Physiol Physiology Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest epithelial malignancies and remains difficult to treat. Pancreatic intraepithelial neoplasias (PanINs) represent the majority of the pre-cancer lesions in the pancreas. The PDAC microenvironment consists of activated pancreatic stellate cells (PSCs) and immune cells, which are thought to contribute to neoplastic transformation. However, the signaling events involved in driving the transition from the neoplastic precursor to the more advanced and aggressive forms in the pancreas are not well understood. Recepteur d’Origine Nantais (RON) is a c-MET family receptor tyrosine kinase that is implicated in playing a role in cell proliferation, migration and other aspects of tumorigenesis. Macrophage stimulating protein (MSP) is the ligand for RON and becomes activated upon proteolytic cleavage by matriptase (also known as ST14), a type II transmembrane serine protease. In the current study, by immunohistochemistry (IHC) analysis of human pancreatic tissues, we found that the expression levels MSP and matriptase are drastically increased during the transition from the preneoplastic PanIN stages to the more advanced and aggressive PDAC. Moreover, RON is highly expressed in both PDAC and in cancer-associated stellate cells. In contrast, MSP, RON, and matriptase are expressed at low levels, if any, in normal pancreas. Our study underscores an emerging role of MSP-RON autocrine and paracrine signaling events in driving malignant progression in the pancreas. Frontiers Media S.A. 2019-02-26 /pmc/articles/PMC6399467/ /pubmed/30863319 http://dx.doi.org/10.3389/fphys.2019.00147 Text en Copyright © 2019 Li, Morvaridi, Lam, Chheda, Kamata, Katsumata, Edderkaoui, Yuan, Nissen, Pandol and Wang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Li, Ce
Morvaridi, Susan
Lam, Gloria
Chheda, Chintan
Kamata, Yoshiko
Katsumata, Makoto
Edderkaoui, Mouad
Yuan, Xiaopu
Nissen, Nicholas
Pandol, Stephen J.
Wang, Qiang
MSP-RON Signaling Is Activated in the Transition From Pancreatic Intraepithelial Neoplasia (PanIN) to Pancreatic Ductal Adenocarcinoma (PDAC)
title MSP-RON Signaling Is Activated in the Transition From Pancreatic Intraepithelial Neoplasia (PanIN) to Pancreatic Ductal Adenocarcinoma (PDAC)
title_full MSP-RON Signaling Is Activated in the Transition From Pancreatic Intraepithelial Neoplasia (PanIN) to Pancreatic Ductal Adenocarcinoma (PDAC)
title_fullStr MSP-RON Signaling Is Activated in the Transition From Pancreatic Intraepithelial Neoplasia (PanIN) to Pancreatic Ductal Adenocarcinoma (PDAC)
title_full_unstemmed MSP-RON Signaling Is Activated in the Transition From Pancreatic Intraepithelial Neoplasia (PanIN) to Pancreatic Ductal Adenocarcinoma (PDAC)
title_short MSP-RON Signaling Is Activated in the Transition From Pancreatic Intraepithelial Neoplasia (PanIN) to Pancreatic Ductal Adenocarcinoma (PDAC)
title_sort msp-ron signaling is activated in the transition from pancreatic intraepithelial neoplasia (panin) to pancreatic ductal adenocarcinoma (pdac)
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399467/
https://www.ncbi.nlm.nih.gov/pubmed/30863319
http://dx.doi.org/10.3389/fphys.2019.00147
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